{"title":"N-Acetylcysteine relieving hydrogen peroxide-induced damage in granulosa cells of sheep.","authors":"Hao Chen, Jine Wang, Bingzhu Zhao, Yahua Yang, Chongfa Yang, Zhijie Zhao, Xiaona Ding, Yang Li, Taojie Zhang, Zhaxi Yingpai, Shengdong Huo","doi":"10.1080/19336918.2025.2484182","DOIUrl":"10.1080/19336918.2025.2484182","url":null,"abstract":"<p><p>Sheep ovarian granulosa cells (GCs) play a unique role in the ovary. Damage to GCs can affect the normal development of oocytes. The oxidative stress model was constructed by H<sub>2</sub>O<sub>2</sub>to study the biological changes. Specifically, pathological characteristic was assessed by immunohistochemistry (IHC), while signaling pathway was studied using western blot, quantitative RT-PCR, and immunofluorescence. Theresults showed that the oxidative damage model was successfully constructed by 200 μmol/LH<sub>2</sub>O<sub>2</sub> for 12 h. NAC can protect the proliferation of GCs under H<sub>2</sub>O<sub>2</sub>-induced oxidative stress and reduce apoptosis. It can also promote the secretion of E<sub>2</sub> and P<sub>4</sub> by GCs and reduce the inflammatory response of GCs. NAC can enhance the expression of NRF2, PI3K and Akt. These findings suggest that NAC alleviates H<sub>2</sub>O<sub>2</sub>-induced oxidative stress injury through NRF2/PI3K/AKT signaling pathways. Provide ideas for studying the poor quality of mammalian oocytes.</p>","PeriodicalId":9680,"journal":{"name":"Cell Adhesion & Migration","volume":"19 1","pages":"2484182"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Redox ReportPub Date : 2025-12-01Epub Date: 2025-05-25DOI: 10.1080/13510002.2025.2498105
Mikaela Peglow Pinz, Isadora Medeiros, Larissa Anastácio da Costa Carvalho, Flavia Carla Meotti
{"title":"Is uric acid a true antioxidant? Identification of uric acid oxidation products and their biological effects.","authors":"Mikaela Peglow Pinz, Isadora Medeiros, Larissa Anastácio da Costa Carvalho, Flavia Carla Meotti","doi":"10.1080/13510002.2025.2498105","DOIUrl":"10.1080/13510002.2025.2498105","url":null,"abstract":"<p><p>Uric acid (UA), the final product of purine metabolism in humans, exhibits a dual role as an anti or pro-oxidant, depending on the microenvironment. The two-electron oxidation of UA by biological oxidants can neutralize such harmful molecules. Additionally, UA chelates metals and can activate adaptive response against oxidation. However, some products of the reaction between UA and oxidants are not inert and, therefore, do not confer the anticipated antioxidant protection. A direct pro-oxidant effect is favoured in the one-electron oxidation of UA by heme-peroxidases yielding free radical intermediates that can initiate or propagate a radical-chain reaction. Additionally, an indirect pro-oxidant effect has been proposed by eliciting the expression or activation of enzymes that catalyse oxidant production, e.g. NADPH oxidase (NOX). This review brings together fundamental concepts and the molecular mechanisms of the redox reactions involving UA. The signature metabolites from these reactions are discussed to give valuable insights on whether these intermediates are being formed and what role they may play in disease pathogenesis. It proposes that, through identifying specific products, it may be possible to elucidate whether a harmful or protective action is linked to downstream bioactivities.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2498105"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-06-10DOI: 10.1080/15592294.2025.2515430
Sarah Costantino, Francesco Paneni
{"title":"Long-lasting metabolic impairment in the failing heart: epigenetic memories at play.","authors":"Sarah Costantino, Francesco Paneni","doi":"10.1080/15592294.2025.2515430","DOIUrl":"10.1080/15592294.2025.2515430","url":null,"abstract":"<p><p>Understanding the factors involved in myocardial recovery after unloading is of utmost importance to unveil new therapies in patients with heart failure (HF). Lack of myocardial recovery might be explained by long-lasting molecular alterations which persist despite normalization of cardiac stress. In this issue of Epigenetics, Roth et al. present an elegant translational study addressing this important aspect at the molecular level. By leveraging a mouse model of reversible transverse aortic constriction (rTAC) and human LV samples from HF patients undergoing LVAD therapy, the authors show that cardiac unloading is associated with a persistent deregulation of transcriptional programmes implicated in mitochondrial respiration, fatty acid and acyl-CoA metabolism, suggesting a long-lasting metabolic deterioration of the failing heart. Of interest, the authors identified several chromatin remodellers (Hdac4, Smarca2, and Brd4) potentially explaining the observed transcriptional alterations. Taken together, these novel findings suggest that 'DNA forgives but does not forget,' thus leaving an epigenetic scar which hampers the recovery of the failing heart after unloading. Disentangling the epigenetic factors involved in such 'transcriptional memory' may set the stage for new interventions resetting the cardiomyocyte transcriptome and myocardial energetics thus fostering a true myocardial recovery in HF.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2515430"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RNA BiologyPub Date : 2025-12-01Epub Date: 2025-06-29DOI: 10.1080/15476286.2025.2506712
Christian Ramirez, Elena Perenthaler, Fabio Lauria, Toma Tebaldi, Gabriella Viero
{"title":"Computational limitations and future needs to unravel the full potential of 2'-O-methylation and C/D box snoRNAs.","authors":"Christian Ramirez, Elena Perenthaler, Fabio Lauria, Toma Tebaldi, Gabriella Viero","doi":"10.1080/15476286.2025.2506712","DOIUrl":"10.1080/15476286.2025.2506712","url":null,"abstract":"<p><p>This review evaluates the current state of C/D snoRNA databases and prediction tools in relation to 2'-O-methylation (2'-O-Me). It highlights the limitations of existing resources in accurately annotating and predicting guide snoRNAs, particularly for newly identified 2'-O-Me sites. We emphasize the need for advanced computational approaches specifically tailored to 2'-O-Me to enable the discovery and functional analysis of snoRNAs. Given the growing importance of 2'-O-Me in areas such as cancer epitranscriptomics, ribosome biogenesis, and heterogeneity, existing tools remain inadequate. As 2'-O-Me gains recognition as a potential biomarker and therapeutic target, more sophisticated methods are urgently needed to improve snoRNA annotation and prediction, facilitating biomedical advancements.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-11"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-07-03DOI: 10.1080/15592294.2025.2527145
Jiawei Li, Wanjun Luo, Daohong Nie, Zidan Lin, Chenfei Zhou
{"title":"Mendelian randomization analysis of CpG methylation and immune phenotypes in epithelial ovarian cancer outcomes.","authors":"Jiawei Li, Wanjun Luo, Daohong Nie, Zidan Lin, Chenfei Zhou","doi":"10.1080/15592294.2025.2527145","DOIUrl":"10.1080/15592294.2025.2527145","url":null,"abstract":"<p><p>Epithelial ovarian cancer (EOC) is a heterogeneous malignancy with distinct histological subtypes, and DNA methylation has emerged as a promising biomarker for early detection. However, the role of methylation patterns in EOC heterogeneity and prognosis remains unclear. In this study, genome-wide association studies (GWAS) data from the Ovarian Cancer Association Consortium (OCAC) and Methylation quantitative trait loci (mQTL) data from the Genetics of DNA Methylation Consortium (GoDMC) were analysed using two-sample Mendelian randomization (MR). We investigated the genetic effects of CpG methylation on the risk and prognosis of five major EOC histotypes. To further explore the mechanisms by which DNA methylation affects EOC outcomes, we performed mediation analysis to evaluate the role of immunophenotypes. Our analysis identified 94 CpG sites associated with high-grade serous ovarian cancer (HGSOC), 9 of which were linked to prognosis. Additional significant associations were found for clear cell, low-grade serous, endometrioid, and mucinous subtypes. Hypomethylation at specific CpG sites was linked to increased EOC risk and shorter survival. Mediation analysis revealed significant interactions between CpG methylation and immunophenotypes, suggesting that immune modulation mediates the effects of DNA methylation on EOC outcomes. These results provide novel insights into the importance of epigenetic and immune-related factors in EOC pathogenesis.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2527145"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12233829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-01-18DOI: 10.1080/15592294.2024.2445447
Wei Zhao, Lisha Lin, Kristen M Kelly, Lauren A Opsasnick, Belinda L Needham, Yongmei Liu, Srijan Sen, Jennifer A Smith
{"title":"Epigenome-wide association study of perceived discrimination in the Multi-Ethnic Study of Atherosclerosis (MESA).","authors":"Wei Zhao, Lisha Lin, Kristen M Kelly, Lauren A Opsasnick, Belinda L Needham, Yongmei Liu, Srijan Sen, Jennifer A Smith","doi":"10.1080/15592294.2024.2445447","DOIUrl":"10.1080/15592294.2024.2445447","url":null,"abstract":"<p><p>Perceived discrimination, recognized as a chronic psychosocial stressor, has adverse consequences on health. DNA methylation (DNAm) may be a potential mechanism by which stressors get embedded into the human body at the molecular level and subsequently affect health outcomes. However, relatively little is known about the effects of perceived discrimination on DNAm. To identify the DNAm sites across the epigenome that are associated with discrimination, we conducted epigenome-wide association analyses (EWAS) of three discrimination measures (everyday discrimination, race-related major discrimination, and non-race-related major discrimination) in 1,151 participants, including 565 non-Hispanic White, 221 African American, and 365 Hispanic individuals, from the Multi-Ethnic Study of Atherosclerosis (MESA). We conducted both race/ethnicity-stratified analyses as well as trans-ancestry meta-analyses. At false discovery rate of 10%, 7 CpGs and 4 differentially methylated regions (DMRs) containing 11 CpGs were associated with perceived discrimination exposures in at least one racial/ethnic group or in meta-analysis. Identified CpGs and/or nearby genes have been implicated in cellular development pathways, transcription factor binding, cancer and multiple autoimmune and/or inflammatory diseases. Of the identified CpGs (7 individual CpGs and 11 within DMRs), two CpGs and one CpG within a DMR were associated with expression of cis genes <i>NDUFS5</i>, <i>AK1RIN1</i>, <i>NCF4</i> and <i>ADSSL1</i>. Our study demonstrated the potential influence of discrimination on DNAm and subsequent gene expression.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2445447"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-06-05DOI: 10.1080/15592294.2025.2506625
Rebekka Roth, Margareta Häckh, Tilman Schnick, Carolin Rommel, Christoph Koentges, Heiko Bugger, Claudia Domisch, Michael R Bristow, Amrut V Ambardekar, Timothy A McKinsey, Ralf Gilsbach, Lutz Hein, Sebastian Preissl
{"title":"Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors.","authors":"Rebekka Roth, Margareta Häckh, Tilman Schnick, Carolin Rommel, Christoph Koentges, Heiko Bugger, Claudia Domisch, Michael R Bristow, Amrut V Ambardekar, Timothy A McKinsey, Ralf Gilsbach, Lutz Hein, Sebastian Preissl","doi":"10.1080/15592294.2025.2506625","DOIUrl":"10.1080/15592294.2025.2506625","url":null,"abstract":"<p><p>Fibrosis, cardiac remodelling, and inflammation are hallmarks of heart failure. To date, there is no available pharmacological cure for heart failure, but mechanical unloading by implantation of a left ventricular assist device (LVAD) can lead to improved cardiac function in a subset of patients. This study aimed to identify the transcriptional response of left ventricular (LV) cardiac myocytes to mechanical unloading in a mouse model of reversible LV pressure overload and in failing human hearts after LVAD implantation. We found that partial recovery of ventricular dysfunction, LV hypertrophy, and gene expression programmes occurred in mice under reversible transverse aortic constriction (rTAC). Gene expression analysis in cardiac myocytes identified a lasting repression of mitochondrial gene expression resulting in compromised fatty acid oxidation in the mouse model of reversible pressure overload and in human LV samples after LVAD therapy and a persistent upregulation of epigenetic and transcriptional regulators. These findings underpin that recovery from heart failure involves complex gene regulatory networks and that mitochondrial dysfunction remains a challenge even after mechanical unloading. Further studies are needed to investigate the functional role of these factors in reverse remodelling and recovery of failing hearts.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2506625"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dual synthesis pathways of scaRNA28 via intronic processing of transformation/transcription domain-associated protein transcripts and a novel independent transcription unit.","authors":"Keiichi Izumikawa, Tatsuya Shida, Hideaki Ishikawa, Sotaro Miyao, Takayuki Ohga, Masato Taoka, Yuko Nobe, Hiroshi Nakayama, Masami Nagahama","doi":"10.1080/15476286.2025.2513133","DOIUrl":"10.1080/15476286.2025.2513133","url":null,"abstract":"<p><p>Small Cajal body-specific RNAs (scaRNAs) are noncoding RNAs involved in the maturation of U-rich small nuclear RNAs. Except for a few that have their own transcription units, most scaRNA genes are embedded in introns and are predicted to be transcribed with host genes. Herein, we report that scaRNA28 is the first scaRNA with a dual synthesis pathway, and that this RNA is transcribed in an independent transcription unit (ITU) by RNA polymerase II while located in intron 2 of the transformation/transcription domain-associated protein (TRRAP) gene. We evaluated the scaRNA28 synthesis pathway using minigenes containing exon 2, intron 2, and exon 3 of <i>TRRAP</i>. A minigene with a mutation preventing 5' splicing recognition of the exon 2/intron 2 junction generated scaRNA28, suggesting a pathway processing unspliced transcripts into scaRNA28. Even promoterless minigenes and DNA fragments with regions from exons 2 to 3 of <i>TRRAP</i> showed RNA polymerase II-dependent synthesis of scaRNA28, indicating a novel synthesis pathway involving an ITU. Linker-scanning mutational analysis revealed that the promoter region required for scaRNA28 expression in the ITU is located within 60 bases including exon 2/intron 2 junction of <i>TRRAP</i>, and especially the first two bases of intron 2 region, a putative part of the MYC-binding (E-box) motif, are essential for scaRNA28 expression in the ITU. MYC promotes scaRNA28 expression by binding to the promoter region in the ITU. Our findings demonstrated a novel transcriptional pathway for the synthesis of scaRNA28, the first scaRNA with a dual synthesis pathway.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Redox ReportPub Date : 2025-12-01Epub Date: 2025-06-09DOI: 10.1080/13510002.2025.2511458
Xiaomei Zhang, Weidong Qiang, Yongxin Guo, Jingli Gong, Huan Yu, Di Wu, Pengxiang Tang, Ma Yidan, Huifeng Zhang, Xin Sun
{"title":"Fucoxanthin alleviates renal aging by regulating the oxidative stress process and the inflammatory response <i>in vitro</i> and <i>in vivo</i> models.","authors":"Xiaomei Zhang, Weidong Qiang, Yongxin Guo, Jingli Gong, Huan Yu, Di Wu, Pengxiang Tang, Ma Yidan, Huifeng Zhang, Xin Sun","doi":"10.1080/13510002.2025.2511458","DOIUrl":"10.1080/13510002.2025.2511458","url":null,"abstract":"<p><strong>Objectives: </strong>Many countries in the world are entering society with an aging population. The kidney is one of the most sensitive organs in the body to aging. Kidney function gradually declines with aging. Renal aging is one of the main triggers of CDK. Therefore, many researchers in the field are looking for natural, green and healthy anti-renal-aging bioactive molecules.</p><p><strong>Methods and results: </strong>Western-blot, ELISA and indirect immunofluorescence were performed to evaluate the biological activity of fucoxanthin against renal aging <i>in vitro</i> and <i>in vivo</i> models. First, in the <i>in vitro</i> model, we evaluated the effect of fucoxanthin on renal cell senescence. We found that fucoxanthin could alleviate the kidney cell senescence caused by H<sub>2</sub>O<sub>2</sub> by detecting a series of senescence markers. In the <i>in vivo</i> model, the experimental results showed that fucoxanthin could alleviate the aging of the kidney by Sa-β-gal staining and detection of aging-related marker molecules. Furthermore, we also found that fucoxanthin could alleviate kidney fibrosis.</p><p><strong>Conclusions: </strong>In this study, our results showed that fucoxanthin was able to alleviate renal aging <i>in vivo</i> and <i>in vitro</i> models, suggesting that fucoxanthin could be a functional food to treat and relieve kidney aging.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2511458"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}